tbuckley/cabot-search huggingface dataset:
Single-cell genomics in acquired bone marrow failure syndromes
Authors: Zhijie Wu, Neal S. Young
Journal: Blood (2023)

Mechanistic studies of immune bone marrow failure are difficult because of the scarcity of residual cells, the involvement of multiple cell types, and the inherent complexities of hematopoiesis and immunity. Single-cell genomic technologies and bioinformatics allow extensive, multidimensional analysis of a very limited number of cells. We review emerging applications of single-cell techniques, and early results related to disease pathogenesis: effector and target cell populations and relationships, cell-autonomous and nonautonomous phenotypes in clonal hematopoiesis, transcript splicing, chromosomal abnormalities, and T-cell receptor usage and clonality. Dense and complex data from single-cell techniques provide insights into pathophysiology, natural history, and therapeutic drug effects.
Bladder-Sparing Treatment With Radical Dose Radiotherapy Is an Effective Alternative to Radical Cystectomy in Patients With Clinically Node-Positive Nonmetastatic Bladder Cancer
Authors: Martin Swinton, Neethu Billy Graham Mariam, Jean Ling Tan, Katherine Murphy, Thiraviyam Elumalai, Manjusha Soni, Alexandra Ferrera, Charlotte Richardson, Richard Walshaw, Hitesh Mistry, Vijay Ramani, Yeepei Song, Alison Birtle, Ann Henry, Joachim Chan, Peter Hoskin, Ananya Choudhury
Journal: Journal of Clinical Oncology (2023)

Bladder-sparing trimodal therapy (TMT) is an alternative to radical cystectomy (RC) according to international guidelines. However, there are limited data to guide management of nonmetastatic clinically node-positive bladder cancer (cN+ M0 BCa). We performed a multicenter retrospective analysis of survival outcomes in node-positive patients to inform practice.
Fabrication and Cell Culture Applications of Core‐Shell Hydrogel Fibers Composed of Chitosan/DNA Interfacial Polyelectrolyte Complexation and Calcium Alginate: Straight and Beaded Core Variations
Authors: Yoshinobu Utagawa, Kosuke Ino, Masahiro Takinoue, Hitoshi Shiku
Journal: Advanced Healthcare Materials (2023)

Core-shell hydrogel fibers are widely used in cell culture applications. A simple and rapid method is presented for fabricating core-shell hydrogel fibers, consisting of straight or beaded core fibers, for cell culture applications. The core fibers are prepared using interfacial polyelectrolyte complexation (IPC) with chitosan and DNA. Briefly, two droplets of chitosan and DNA are brought in contact to form an IPC film, which is dragged to prepare an IPC fiber. The incubation time and DNA concentration are adjusted to prepare straight and beaded IPC fibers. The fibers with Ca
The Promise of Quantitative Computed Tomographic Analysis in Assessing Progression of Interstitial Lung Abnormalities and Emphysema in Smokers
Authors: Anna Rita Larici, Giuseppe Cicchetti
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"The Promise of Quantitative CT Analysis in Assessing Progression of ILA and Emphysema in Smokers.." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Retraction: Altered store operated calcium entry increases cyclic 3′,5′-adenosine monophosphate production and extracellular signal-regulated kinases 1 and 2 phosphorylation in polycystin-2-defective cholangiocytes
Journal: Hepatology (2023)

Retraction Manuscript for DOI: 10.1002/hep.24723 https://journals.lww.com/hep/Fulltext/2012/03000/Altered_store_operated_calcium_entry_increases.22.aspx
Prospective Correlation of Magnetic Resonance Tumor Regression Grade With Pathologic Outcomes in Total Neoadjuvant Therapy for Rectal Adenocarcinoma
Authors: William A. Hall, Jiahe Li, Y. Nancy You, Marc J. Gollub, Joseph R. Grajo, Mark Rosen, Greg dePrisco, Greg Yothers, Jennifer A. Dorth, Osama E. Rahma, Marcia M. Russell, Howard M. Gross, Samuel A. Jacobs, Bryan A. Faller, Sagila George, Tareq Al baghdadi, Michael G. Haddock, Richard Valicenti, Theodore S. Hong, Thomas J. George
Journal: Journal of Clinical Oncology (2023)

Total neoadjuvant therapy (TNT) is a newly established standard treatment for rectal adenocarcinoma. Current methods to communicate magnitudes of regression during TNT are subjective and imprecise. Magnetic resonance tumor regression grade (MR-TRG) is an existing, but rarely used, regression grading system. Prospective validation of MR-TRG correlation with pathologic response in patients undergoing TNT is lacking. Utility of adding diffusion-weighted imaging to MR-TRG is also unknown.
Retraction: Protein kinase a-dependent pSer675-β-catenin, a novel signaling defect in a mouse model of congenital hepatic fibrosis
Journal: Hepatology (2023)

Retraction Manuscript for DOI: 10.1002/hep.26554 https://journals.lww.com/hep/Fulltext/2013/11000/Protein_kinase_a_dependent_pSer675___catenin,_a.21.aspx
A Skin Care Program to Prevent Skin Problems due to Diabetes Devices in Children and Adolescents: A Cluster-Controlled Intervention Study
Authors: Anna Korsgaard Berg, Annemarie Cecilie Grauslund, Fiona Sørensen, Steffen Ullitz Thorsen, Jacob P. Thyssen, Claus Zachariae, Jannet Svensson
Journal: Diabetes Care (2023)

OBJECTIVE Diabetes devices that deliver insulin and measure blood glucose levels are cornerstones in modern treatment of type 1 diabetes. However, their use is frequently associated with the development of skin problems, particularly eczema and wounds. Proper skin care may prevent skin problems, yet evidence-based information from interventional studies is missing. Providing this information is the aim of this study. RESEARCH DESIGN AND METHODS This cluster-controlled intervention study tested the efficacy of a basic skin care program (including use of lipid cream, removal, and avoidance of disinfection). A total of 170 children and adolescents with type 1 diabetes were included and assigned either to the intervention group (n = 112) or the control group (n = 58). Participants were seen quarterly the first year after device initiation, with clinical assessment and interview in an unblinded setting. RESULTS Eczema or wounds were observed in 33.6% of the intervention group compared with 46.6% of control participants (absolute difference, 12.9% [95% CI −28.7%, 2.9%]; P = 0.10). The adjusted odds of wound development were decreased by 71% in the intervention compared with control group (for wounds, odds ratio 0.29 [95% CI 0.12, 0.68]; P = 0.005). In total, only eight infections were seen, without a higher frequency in the intervention group, despite advice to omit disinfection. CONCLUSIONS These data indicate our basic skin care program partially prevented diabetes device–induced skin reactions. However, more preventive strategies with other adhesives, patches, and/or types of lotions are needed for optimized prevention.
Addressing the Use of the CAPTURE (a Chronic Obstructive Pulmonary Disease Screening Tool) in Chronic Obstructive Pulmonary Disease Treatment Decisions
Authors: Barbara P. Yawn, Susan Murray
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Addressing the Use of the CAPTURE (A COPD Screening Tool) in COPD Treatment Decisions." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Platelet count threshold for hemorrhage in patients with immune thrombocytopenia treated with antiplatelet agents
Authors: Natasha Ollier, Marie-Léa Piel-Julian, Matthieu Mahévas, Jean-François Viallard, Thibault Comont, Stéphane Chèze, Sylvain Audia, Mikaël Ebbo, Louis Terriou, Jean-Christophe Lega, Pierre-Yves Jeandel, Bernard Bonnotte, Marc Michel, Maryse Lapeyre-Mestre, Bertrand Godeau, Guillaume Moulis
Journal: Blood (2023)
How I treat non-transfusion-dependent β-thalassemia
Authors: Antoine N. Saliba, Khaled M. Musallam, Ali T. Taher
Journal: Blood (2023)

The intricate interplay of anemia and iron overload under the pathophysiological umbrella of ineffective erythropoiesis in non-transfusion-dependent β-thalassemia (NTDT) results in a complex variety of clinical phenotypes that are challenging to diagnose and manage. In this article, we use a clinical framework rooted in pathophysiology to present 4 common scenarios of patients with NTDT. Starting from practical considerations in the diagnosis of NTDT, we delineate our strategy for the longitudinal care of patients who exhibit different constellations of symptoms and complications. We highlight the use of transfusion therapy and novel agents, such as luspatercept, in the patient with anemia-related complications. We also describe our approach to chelation therapy in the patient with iron overload. Although tackling every specific complication of NTDT is beyond the scope of this article, we touch on the management of the various morbidities and multisystem manifestations of the disease.
Assessment of Meal Anticipation for Improving Fully Automated Insulin Delivery in Adults With Type 1 Diabetes
Authors: Jose Garcia-Tirado, Patricio Colmegna, Orianne Villard, Jenny L. Diaz, Rebeca Esquivel-Zuniga, Chaitanya L. K. Koravi, Charlotte L. Barnett, Mary C. Oliveri, Morgan Fuller, Sue A. Brown, Mark D. DeBoer, Marc D. Breton
Journal: Diabetes Care (2023)

Meals are a consistent challenge to glycemic control in type 1 diabetes (T1D). Our objective was to assess the glycemic impact of meal anticipation within a fully automated insulin delivery (AID) system among adults with T1D.We report the results of a randomized crossover clinical trial comparing three modalities of AID systems: hybrid closed loop (HCL), full closed loop (FCL), and full closed loop with meal anticipation (FCL+). Modalities were tested during three supervised 24-h admissions, where breakfast, lunch, and dinner were consumed per participant's home schedule, at a fixed time, and with a 1.5-h delay, respectively. Primary outcome was the percent time in range 70-180 mg/dL (TIR) during the breakfast postprandial period for FCL+ versus FCL.Thirty-five adults with T1D (age 44.5 ± 15.4 years; HbA1c 6.7 ± 0.9%; n = 23 women and n = 12 men) were randomly assigned. TIR for the 5-h period after breakfast was 75 ± 23%, 58 ± 21%, and 63 ± 19% for HCL, FCL, and FCL+, respectively, with no significant difference between FCL+ and FCL. For the 2 h before dinner, time below range (TBR) was similar for FCL and FCL+. For the 5-h period after dinner, TIR was similar for FCL+ and FCL (71 ± 34% vs. 72 ± 29%; P = 1.0), whereas TBR was reduced in FCL+ (median 0% [0-0%] vs. 0% [0-0.8%]; P = 0.03). Overall, 24-h control for HCL, FCL, and FCL+ was 86 ± 10%, 77 ± 11%, and 77 ± 12%, respectively.Although postprandial control remained optimal with hybrid AID, both fully AID solutions offered overall TIR >70% with similar or lower exposure to hypoglycemia. Anticipation did not significantly improve postprandial control in AID systems but also did not increase hypoglycemic risk when meals were delayed.
When I use a word . . . Medical slang: gomers and gomerettes
Authors: Jeffrey K Aronson
Journal: BMJ (2023)

The medical slang term “gomer,” variously defined, refers pejoratively to a patient who is down and out and often admitted to hospital with untreatable conditions. The origin of the term is unknown, but it is generally thought to be a reference to a character called Gomer Pyle who appeared in American sitcoms in the 1960s. The many derivatives of gomer include gomer doc (a physician who hasn’t kept up with recent medical developments), gomer extraordinaire, gomerism, gomeroid, gomertose (a comatose gomer), and gomere or gomerette (a female gomer). They tend to be extensively investigated, resulting in gomergrams. The term, principally American, is to be avoided.
Preoperative Prediction of Microvascular Invasion with Gadoxetic Acid-Enhanced Magnetic Resonance Imaging in Patients with Single Hepatocellular Carcinoma: The Implication of Surgical Decision on the Extent of Liver Resection
Authors: Na Reum Kim, Heejin Bae, Hyeo Seong Hwang, Dai Hoon Han, Kyung Sik Kim, Jin Sub Choi, Mi-Suk Park, Gi Hong Choi
Journal: Liver Cancer (2023)

Microvascular invasion (MVI) is one of the most important prognostic factors for hepatocellular carcinoma (HCC) recurrence, but its application in preoperative clinical decisions is limited. This study aimed to identify preoperative predictive factors for MVI in HCC and further evaluate oncologic outcomes of different types and extents of hepatectomy according to stratified risk of MVI.
Changes to healthcare utilisation and symptoms for common mental health problems over the first 21 months of the COVID-19 pandemic: parallel analyses of electronic health records and survey data in England
Authors: Vicky P. Taxiarchi, Morwenna Senior, Darren M. Ashcroft, Matthew J. Carr, Holly Hope, Matthew Hotopf, Evangelos Kontopantelis, Sally McManus, Praveetha Patalay, Sarah Steeg, Roger T. Webb, Kathryn M. Abel, Matthias Pierce
Journal: The Lancet Regional Health - Europe (2023)

Few studies have investigated the effect of the COVID-19 pandemic on mental health beyond 2020. This study quantifies changes to healthcare utilisation and symptoms for common mental health problems over the pandemic's first 21 months.Parallel cohort studies using primary care database and survey data for adults (≥16 years) in England from January 2015 to December 2021: 16,551,842 from the Clinical Practice Research Datalink (CPRD) and 40,699 from the UK Household Longitudinal Survey (UKHLS). Interrupted time-series models estimated changes in monthly prevalence of presentations and prescribed medications for anxiety and depression (CPRD); and self-reported psychological distress (UKHLS). The pandemic period was divided into five phases: 1st Wave (April-May 2020); post-1st Wave (June-September 2020); 2nd Wave (October 2020-February 2021); post 2nd Wave (March-May 2021); 3rd Wave (June-December 2021).Primary care presentations for depression or anxiety dropped during the first wave (4.6 fewer monthly appointments per 1000 patients, 4.4-4.8) and remained lower than expected throughout follow-up. Self-reported psychological distress exceeded expected levels during the first (Prevalence Ratio = 1.378, 95% CI 1.289-1.459) and second waves (PR = 1.285, 1.189-1.377), returning towards expected levels during the third wave (PR = 1.038, 0.929-1.154). Increases in psychological distress and declines in presentations were greater for women. The decrease in primary care presentations for depression and anxiety exceeded that for physical health conditions (rheumatoid arthritis, diabetes, urinary tract infections). Anxiety and depression prescriptions returned to pre-pandemic levels during the second wave due to increased repeat prescriptions.Despite periods of distress during the pandemic, we did not find an enduring effect on common mental health problems. The fall in primary care presentations for anxiety or depression suggests changing healthcare utilisation for mental distress and a potential treatment gap.National Institute for Health and Care Research (NIHR).
Presurgical 68Ga-PSMA-11 Positron Emission Tomography for Biochemical Recurrence Risk Assessment: A Follow-up Analysis of a Multicenter Prospective Phase 3 Imaging Trial
Authors: Loïc Djaïleb, Wesley R. Armstrong, Daniel Thompson, Andrei Gafita, Andrea Farolfi, Abhejit Rajagopal, Tristan R. Grogan, Kathleen Nguyen, Matthias R. Benz, Masatoshi Hotta, Francesco Barbato, Francesco Ceci, Sarah M. Schwarzenböck, Marcus Unterrainer, Helle D. Zacho, Roxanna Juarez, Matthew Cooperberg, Peter Carroll, Samuel Washington, Robert E. Reiter, Matthias Eiber, Ken Herrmann, Wolfgang P. Fendler, Johannes Czernin, Thomas A. Hope, Jeremie Calais
Journal: European Urology (2023)
Highlights from FEMS 2023
Authors: Mariano A Molina
Journal: The Lancet Microbe (2023)

Between July 9 and July 13, 2023, the 10th Federation of European Microbiological Societies (FEMS) Congress was held in Hamburg, Germany. This iteration of the biennial FEMS Congress was co-organised by two German microbiology societies: the VAAM (Association for General and Applied Microbiology) and DGHM (German Society of Hygiene and Microbiology).
Lipoprotein(a) and carotid intima-media thickness in children with familial hypercholesterolaemia in the Netherlands: a 20-year follow-up study
Authors: Lotte M de Boer, Albert Wiegman, Jeffrey Kroon, Sotirios Tsimikas, Calvin Yeang, Merel C Peletier, Alma Revers, John J P Kastelein, Aeilko H Zwinderman, Barbara A Hutten
Journal: The Lancet Diabetes & Endocrinology (2023)
Combined AAV-mediated gene replacement therapy improves auditory function in a mouse model of human DFNB42 deafness
Authors: Kevin Isgrig, Alexander X. Cartagena-Rivera, Hong Jun Wang, Mhamed Grati, Katharine A. Fernandez, Thomas B. Friedman, Inna A. Belyantseva, Wade Chien
Journal: Molecular Therapy (2023)

Hearing loss is a common disorder affecting nearly 20% of the world's population. Recently, studies have shown that inner ear gene therapy can improve auditory function in several mouse models of hereditary hearing loss. In most of these studies, the underlying mutations affect only a small number of cell types of the inner ear (e.g., sensory hair cells). Here, we applied inner ear gene therapy to the Ildr1
Novel MECP2 gene therapy is effective in a multicenter study using two mouse models of Rett syndrome and is safe in non-human primates
Authors: Samantha Powers, Shibi Likhite, Kamal K. Gadalla, Carlos J. Miranda, Amy J. Huffenberger, Cassandra Dennys, Kevin D. Foust, Pablo Morales, Christopher R. Pierson, Federica Rinaldi, Stephanie Perry, Brad Bolon, Nicolas Wein, Stuart Cobb, Brian K. Kaspar, Kathrin C. Meyer
Journal: Molecular Therapy (2023)

The AAV9 gene therapy vector presented in this study is safe in mice and non-human primates and highly efficacious without causing overexpression toxicity, a major challenge for clinical translation of Rett syndrome gene therapy vectors to date. Our team designed a new truncated methyl-CpG-binding protein 2 (MECP2) promoter allowing widespread expression of MECP2 in mice and non-human primates after a single injection into the cerebrospinal fluid without causing overexpression symptoms up to 18 months after injection. Additionally, this new vector is highly efficacious at lower doses compared with previous constructs as demonstrated in extensive efficacy studies performed by two independent laboratories in two different Rett syndrome mouse models carrying either a knockout or one of the most frequent human mutations of Mecp2. Overall, data from this multicenter study highlight the efficacy and safety of this gene therapy construct, making it a promising candidate for first-in-human studies to treat Rett syndrome. The AAV9 gene therapy vector presented in this study is safe in mice and non-human primates and highly efficacious without causing overexpression toxicity, a major challenge for clinical translation of Rett syndrome gene therapy vectors to date. Our team designed a new truncated methyl-CpG-binding protein 2 (MECP2) promoter allowing widespread expression of MECP2 in mice and non-human primates after a single injection into the cerebrospinal fluid without causing overexpression symptoms up to 18 months after injection. Additionally, this new vector is highly efficacious at lower doses compared with previous constructs as demonstrated in extensive efficacy studies performed by two independent laboratories in two different Rett syndrome mouse models carrying either a knockout or one of the most frequent human mutations of Mecp2. Overall, data from this multicenter study highlight the efficacy and safety of this gene therapy construct, making it a promising candidate for first-in-human studies to treat Rett syndrome.
Dual-locus, dual-HDR editing permits efficient generation of antigen-specific regulatory T cells with robust suppressive activity
Authors: Martina S. Hunt, Soo Jung Yang, Emma Mortensen, Ahmad Boukhris, Jane Buckner, Peter J. Cook, David J. Rawlings
Journal: Molecular Therapy (2023)

Adoptive regulatory T (Treg) cell therapy is predicted to modulate immune tolerance in autoimmune diseases, including type 1 diabetes (T1D). However, the requirement for antigen (ag) specificity to optimally orchestrate tissue-specific, Treg cell-mediated tolerance limits effective clinical application. To address this challenge, we present a single-step, combinatorial gene editing strategy utilizing dual-locus, dual-homology-directed repair (HDR) to generate and specifically expand ag-specific engineered Treg (EngTreg) cells derived from donor CD4+ T cells. Concurrent delivery of CRISPR nucleases and recombinant (r)AAV homology donor templates targeting FOXP3 and TRAC was used to achieve three parallel goals: enforced, stable expression of FOXP3; replacement of the endogenous T cell receptor (TCR) with an islet-specific TCR; and selective enrichment of dual-edited cells. Each HDR donor template contained an alternative component of a heterodimeric chemically inducible signaling complex (CISC), designed to activate interleukin-2 (IL-2) signaling in response to rapamycin, promoting expansion of only dual-edited EngTreg cells. Using this approach, we generated purified, islet-specific EngTreg cells that mediated robust direct and bystander suppression of effector T (Teff) cells recognizing the same or a different islet antigen peptide, respectively. This platform is broadly adaptable for use with alternative TCRs or other targeting moieties for application in tissue-specific autoimmune or inflammatory diseases.
Inhibition of complement C3 signaling ameliorates locomotor and visual dysfunction in autoimmune inflammatory diseases
Authors: Li Xu, Huiming Xu, Siqi Chen, Wei Jiang, Shabbir Khan Afridi, Yuge Wang, Xin Ren, Yipeng Zhao, Shuiqing Lai, Xiusheng Qiu, Yu-Wen Alvin Huang, Yaxiong Cui, Hui Yang, Wei Qiu, Changyong Tang
Journal: Molecular Therapy (2023)
Efficient T cell adoptive transfer in lymphoreplete hosts mediated by transient activation of Stat5 signaling
Authors: Megan D. Tennant, Christina New, Leonardo M.R. Ferreira, Richard T. O’Neil
Journal: Molecular Therapy (2023)

Lymphodepleting pre-conditioning is a nearly universal component of T cell adoptive transfer protocols. The side effects of pre-conditioning regimens used in adoptive cell therapy are clinically significant and include pan-cytopenia, immune suppression, and reactive myelopoiesis. We conducted studies to test the hypothesis that the mechanisms underlying effective engraftment are cell autonomous and not dependent on a lymphodepleted host immune status. These studies leveraged mouse models to examine the role of Stat5 signaling during T cell adoptive transfer. We observed that, by transiently expressing a constitutively active mutamer of Stat5b during the process of adoptive transfer, we could completely obviate the need for lymphodepletion prior to adoptive transfer. Using several functional assays, we benchmark the function of the engrafted T cells against T cells transferred after conventional lymphodepletion. These studies identify a cell-autonomous mechanism driven by transient Stat5b signaling with lasting effects on T cell phenotype and function. Furthermore, the results presented suggest that adoptive T cell therapy could be improved by removing lymphodepletion protocols entirely and replacing them with RNA transfection of T cells with transcripts encoding active Stat5.
Recent advances in the treatment of tuberculosis
Authors: Ilaria Motta, Martin Boeree, Dumitru Chesov, Keertan Dheda, Gunar Günther, Charles Robert Horsburgh, Yousra Kherabi, Christoph Lange, Christian Lienhardt, Helen M. McIlleron, Nicholas I. Paton, Helen R. Stagg, Guy Thwaites, Zarir Udwadia, Reinout Van Crevel, Gustavo E. Velásquez, Robert J. Wilkinson, Lorenzo Guglielmetti, Ilaria Motta, Yousra Kherabi, Reinout Van Crevel, Lorenzo Guglielmetti
Journal: Clinical Microbiology and Infection (2023)
5-MTHF enhances the portal pressure reduction achieved with propranolol in patients with cirrhosis: A randomized placebo-controlled trial
Authors: Ranka Vukotic, Roberto Di Donato, Greta Roncarati, Patrizia Simoni, Matteo Renzulli, Stefano Gitto, Filippo Schepis, Erica Villa, Annalisa Berzigotti, Jaume Bosch, Pietro Andreone
Journal: Journal of Hepatology (2023)